In cervical cancer, the third most common cancer among women worldwide, human papillomaviruses (HPV) play a causative role. Most preventive and therapeutic vaccine developments against HPV are concentrated on HPV16 since it is linked to about 50% of cervical cancer. HPV18 is second in rank with respect to frequency worldwide at 14% of cases but predominates in Asian women as well as in cervical adeno and adenosquamous carcinomas which are the most aggressive type of cervical carcinomas and therefore also warrants research efforts. HPV virus like particles (VLP) consisting of the capsid protein L1 have emerged as the leading preventive vaccine strategy for HPV associated lesions. However, they are unlikely to have effects in the millions of women that are already infected or have developed cervical cancer. Immunization with chimeric HPV VLP expressing the early HPV gene products E6/E7 has therapeutic potential since these gene products are maintained even at late stages of cervical cancer but the induction of neutralizing antibodies against the capsid protein limits their therapeutic capacity. They are, however, powerful tools for induction of T cell responses against early HPV gene product and antigenic peptide mapping. Based on these characteristics we propose to explore the following aims: 1) The use of HPV VLP for inducing human T cell responses to human endogenously presented antigenic epitopes of HPV18 E6/E7 proteins and for generating HPV18 specific T cell clones. 2) in order to avoid the effects of neutralizing antibodies, transferring HPV16 or 18 E6 or E7 specific T cell reactivity induced by chimeric HPV VLP to alternate human effector cells, and 3) the same as aim 2 but now transferring their reactivity to alternate mouse effector cells, To achieve these aims the following methods will be used: 1) in vitro immunization of human peripheral blood T cells with autologous DC loaded with HPV VLP expressing HPV18 E6/E7 protein. 2) identify and clone the HPV16 or 18 specific TCR genes obtained from the chimeric HPV VLP induced T cells and transferring them to alternate human T cells, and 3) the same as in aim 2 but transferring the TCRs to mouse T cells and testing their antitumor activity in vivo. These combined aims will increase the potential of chimeric HPV VLP for treatment of cervical cancer which is our long term objective.